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1.
Genet Mol Biol ; 47(2): e20230347, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38985013

RESUMO

Cigarette smoke (CS) has been generally recognized as a chief carcinogenic factor in renal cell carcinoma (RCC). The stimulative effect of CS on renal cancer stem cells (RCSCs) has been described previously. The Sonic Hedgehog (SHH) pathway plays an essential role in self-renewal, cell growth, drug resistance, metastasis, and recurrence of cancer stem cells (CSCs). Renal cancer-related gene ΔNp63α is highly expressed in renal epithelial tissues and contributes to the RCSCs characteristics of tumors. The aim of this study was to elucidate the role of ΔNp63α and the SHH pathway on the activity of RCSCs induced by CS through a series of in vivo and in vitro studies. It was shown that in renal cancer tissues, ΔNp63α and RCSCs markers in smokers are expressed higher than that in non-smokers. RCSCs were effectively enriched by tumor sphere formation assay. Besides, CS increased the expression of RCSCs markers and the capability of sphere-forming in vitro and in vivo. Moreover, the SHH pathway was activated, and the specialized inhibitor alleviated the promotion of CS on RCSCs. ΔNp63α activated the SHH pathway and promoted CS-induced enhancement of RCSCs activity. These findings indicate that ΔNp63α positively regulates the activity of CS-induced RCSCs via the SHH pathway.

2.
Phys Rev Lett ; 132(26): 261903, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38996282

RESUMO

We perform a simultaneous global analysis of hadron fragmentation functions (FFs) to various charged hadrons (π^{±}, K^{±}, and p/p[over ¯]) at next-to-leading order in QCD. The world data include results from electron-positron single-inclusive annihilation, semi-inclusive deep inelastic scattering, as well as proton-proton collisions including jet fragmentation measurements for the first time, which lead to strong constraints on the gluon fragmentations. By carefully selecting hadron kinematics to ensure the validity of QCD factorization and the convergence of perturbative calculations, we achieve a satisfying best fit with χ^{2}/d.o.f.=0.90. The total momentum of u, d quarks and gluon carried by light charged hadrons have been determined precisely, urging precision determinations of FFs to neutral hadrons for a test of fundamental sum rules in QCD fragmentation.

3.
Cardiovasc Diabetol ; 23(1): 273, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39049086

RESUMO

BACKGROUND: Extracellular matrix (ECM) stiffness is closely related to the progress of diabetic cardiomyopathy (DCM) and the response of treatment of DCM to anti-diabetic drugs. Dapagliflozin (Dapa) has been proven to have cardio-protective efficacy for diabetes and listed as the first-line drug to treat heart failure. But the regulatory relationship between ECM stiffness and treatment efficacy of Dapa remains elusive. MATERIALS AND METHODS: This work investigated the effect of ECM stiffness on DCM progression and Dapa efficacy using both in vivo DCM rat model and in vitro myocardial cell model with high glucose injury. First, through DCM rat models with various levels of myocardial injury and administration with Dapa treatment for four weeks, the levels of myocardial injury, myocardial oxidative stress, expressions of AT1R (a mechanical signal protein) and the stiffness of myocardial tissues were obtained. Then for mimicking the stiffness of myocardial tissues at early and late stages of DCM, we constructed cell models through culturing H9c2 myocardial cells on the polyacrylamide gels with two stiffness and exposed to a high glucose level and without/with Dapa intervention. The cell viability, reactive oxygen species (ROS) levels and expressions of mechanical signal sensitive proteins were obtained. RESULTS: The DCM progression is accompanied by the increased myocardial tissue stiffness, which can synergistically exacerbate myocardial cell injury with high glucose. Dapa can improve the ECM stiffness-induced DCM progression and its efficacy on DCM is more pronounced on the soft ECM, which is related to the regulation pathway of AT1R-FAK-NOX2. Besides, Dapa can inhibit the expression of the ECM-induced integrin ß1, but without significant impact on piezo 1. CONCLUSIONS: Our study found the regulation and effect of biomechanics in the DCM progression and on the Dapa efficacy on DCM, providing the new insights for the DCM treatment. Additionally, our work showed the better clinical prognosis of DCM under early Dapa intervention.


Assuntos
Compostos Benzidrílicos , Cardiomiopatias Diabéticas , Matriz Extracelular , Glucosídeos , Miócitos Cardíacos , Estresse Oxidativo , Ratos Sprague-Dawley , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Cardiomiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/patologia , Glucosídeos/farmacologia , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/patologia , Compostos Benzidrílicos/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Miócitos Cardíacos/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Espécies Reativas de Oxigênio/metabolismo , Ratos , Quinase 1 de Adesão Focal/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações
4.
Soc Sci Med ; 356: 117136, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39047519

RESUMO

RATIONALE: The escalating dissemination of health misinformation on social media platforms poses a significant threat to users' well-being. It is imperative to identify the types of health misinformation that are more susceptible to widespread dissemination and to explore strategies to curb its spread. METHOD: This study designed a 2 (emotional appeal type: positive vs. negative) × 2 (fabricated source type: pseudo-common vs. pseudo-authoritative) × 2 (accuracy-nudge label: No vs. Yes) online between-subjects experiment controlling for factors such as e-health literacy, prior sharing experience, and personal involvement. A snowball sampling approach was used to recruit 1952 participants through social media, resulting in a final sample of 1393 valid responses. RESULTS: Compared to positive emotional appeal and pseudo-common sources, negative emotional appeal and pseudo-authoritative sources resulted in higher levels of sharing intention. Under the condition of negative emotional appeal, the promotion effect of pseudo-authoritative sources on sharing intention was intensified. The accuracy-nudge intervention could significantly mitigate this tendency. The underlying mechanisms revealed more details: both negative emotional appeals and pseudo-authoritative sources increased the perceived credibility of health misinformation, thereby increasing users' sharing intention. However, in contrast to pseudo-authoritative sources, excessive negative emotional appeal induced vigilant verification behavior among users, which reduced sharing to some extent. Adding an accuracy-nudge label to health misinformation reduced users' misguided trust in health misinformation features and stimulated information verification, ultimately reducing health misinformation sharing intention. CONCLUSIONS: Negative emotional appeal and pseudo-authoritative sources can enhance the perceived credibility of health misinformation, thereby strengthening the sharing intention of social media users. Therefore, health misinformation with negative emotional appeal and pseudo-authoritative sources is more likely to be widely shared. The accuracy nudge intervention can trigger users' information verification behavior, suppress the persuasive effects of the misinformation features mentioned above, and help prevent the spread of health misinformation on social media.

5.
Biotechnol Prog ; : e3493, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953182

RESUMO

Total sialic acid content (TSA) in biotherapeutic proteins is often a critical quality attribute as it impacts the drug efficacy. Traditional wet chemical assays to quantify TSA in biotherapeutic proteins during cell culture typically takes several hours or longer due to the complexity of the assay which involves isolation of sialic acid from the protein of interest, followed by sample preparation and chromatographic based separation for analysis. Here, we developed a machine learning model-based technology to rapidly predict TSA during cell culture by using typically measured process parameters. The technology features a user interface, where the users only have to upload cell culture process parameters as input variables and TSA values are instantly displayed on a dashboard platform based on the model predictions. In this study, multiple machine learning algorithms were assessed on our dataset, with the Random Forest model being identified as the most promising model. Feature importance analysis from the Random Forest model revealed that attributes like viable cell density (VCD), glutamate, ammonium, phosphate, and basal medium type are critical for predictions. Notably, while the model demonstrated strong predictability by Day 14 of observation, challenges remain in forecasting TSA values at the edges of the calibration range. This research not only emphasizes the transformative power of machine learning and soft sensors in bioprocessing but also introduces a rapid and efficient tool for sialic acid prediction, signaling significant advancements in bioprocessing. Future endeavors may focus on data augmentation to further enhance model precision and exploration of process control capabilities.

6.
Water Res ; 261: 121983, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38924951

RESUMO

The migration and dissemination of antibiotics and their corresponding antibiotic resistance genes (ARGs) from pharmaceutical plants through wastewater treatment to the environment introduce exogenous ARGs, increasing the risk of antibiotic resistance. Cephalosporin antibiotics (Ceps) are among the most widely used antibiotics with the largest market scale today, and the issue of resistance is becoming increasingly severe. In this study, a cephalosporin pharmaceutical plant was selected and metagenomic analysis was employed to investigate the dissemination patterns of cephalosporin antibiotics (Ceps) and their ARGs (CepARGs) from the pharmaceutical plant through the wastewater treatment plant to tidal flats sediments. The findings revealed a significant reduction in the total concentration of Ceps by 90.32 % from the pharmaceutical plant's Pioneer Bio Reactor (PBR) to the effluent of the wastewater treatment plant, and a notable surge of 172.13 % in the relative abundance of CepARGs. It was observed that CepARGs originating from the PBR could migrate along the dissemination chain, contributing to 60 % of the CepARGs composition in tidal flats sediments. Microorganisms play a crucial role in the migration of CepARGs, with efflux-mediated CepARGs, as an intrinsic resistance mechanism, exhibiting a higher prospensity for migration due to their presence in multiple hosts. While Class I risk CepARGs are present at the pharmaceutical and wastewater plant stages, Class I ina-CepARGs are completely removed during wastewater treatment and do not migrate to the environment. This study reveals the dynamic migration characteristics and potential risk changes regarding Ceps and CepARGs in real dissemination chains, providing new theoretical evidence for the mitigation, control, and risk prevention of CepARGs.

7.
Front Pharmacol ; 15: 1374669, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895626

RESUMO

Pulmonary fibrosis is a progressive, irreversible, chronic interstitial lung disease associated with high morbidity and mortality rates. Current clinical drugs, while effective, do not reverse or cure pulmonary fibrosis and have major side effects, there are urgent needs to develop new anti-pulmonary fibrosis medicine, and corresponding industrially scalable process as well. Salvia castanea Diels f. tomentosa Stib., a unique herb in Nyingchi, Xizang, China, is a variant of S. castanea. and its main active ingredient is rosmarinic acid (RA), which can be used to prepare methyl rosmarinate (MR) with greater drug potential. This study presented an industrially scalable process for the preparation of MR, which includes steps such as polyamide resin chromatography, crystallization and esterification, using S. castanea Diels f. tomentosa Stib. as the starting material and the structure of the product was verified by NMR technology. The anti-pulmonary fibrosis effects of MR were further investigated in vivo and in vitro. Results showed that this process can easily obtain high-purity RA and MR, and MR attenuated bleomycin-induced pulmonary fibrosis in mice. In vitro, MR could effectively inhibit TGF-ß1-induced proliferation and migration of mouse fibroblasts L929 cells, promote cell apoptosis, and decrease extracellular matrix accumulation thereby suppressing progressive pulmonary fibrosis. The anti-fibrosis effect of MR was stronger than that of the prodrug RA. Further study confirmed that MR could retard pulmonary fibrosis by down-regulating the phosphorylation of the TGF-ß1/Smad and MAPK signaling pathways. These results suggest that MR has potential therapeutic implications for pulmonary fibrosis, and the establishment of this scalable preparation technology ensures the development of MR as a new anti-pulmonary fibrosis medicine.

8.
ACS Appl Mater Interfaces ; 16(21): 27761-27766, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38748552

RESUMO

Surface-initiated iron(0)-mediated controlled radical polymerization (SI-Fe0CRP) with low toxicity and excellent biocompatibility is promising for the fabrication of biofunctional polymer coatings. However, the development of Fe(0)-based catalysts remains limited by the lower dissociation activity of the Fe(0) surface in comparison to Cu(0). Here, we found that, by simply polishing the Fe(0) plate surface with sandpaper, the poly(methacryloyloxy)ethyl trimethylammonium chloride brush growth rate has been increased significantly to 3.3 from 0.14 nm min-1 of the pristine Fe(0) plate. The excellent controllability of roughness-mediated SI-Fe0CRP can be demonstrated by customizing multicompartment brushes and triblock brushes. Furthermore, we found that the resulting polymer brush coatings exhibit remarkably low water adhesion (0.097 mN) and an outstanding drag reduction rate of 52% in water. This work provides a promising strategy for regulating the grafting rate of polymer brushes via SI-Fe0CRP for biocompatible marine drag reduction coatings.

9.
Biotechnol Prog ; : e3477, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38699906

RESUMO

Media preparation parameters contribute significantly to media quality, cell culture performance, productivity, and product quality. Establishing proper media preparation procedures is critical for ensuring a robust CHO cell culture process. Process analytical technology (PAT) enables unique ways to quantify assessments and improve media quality. Here, cell culture media were prepared under a wide range of temperatures (40-80°C) and pH (7.6-10.0). Media quality profiles were compared using three real-time PATs: Fourier-transform infrared (FTIR) spectroscopy, Raman spectroscopy, and excitation-emission matrix (EEM) spectroscopy. FTIR and Raman spectroscopies identified shifts in media quality under high preparation temperature (80°C) and at differing preparation pH which negatively impacted monoclonal antibody (mAb) production. In fed-batch processes for production of three different mAbs, viable cell density (VCD) and cell viability were mostly unaffected under all media preparation temperatures, while titer and cell specific productivity of mAb decreased when cultured in basal and feed media prepared at 80°C. High feed preparation pH alone was tolerated but cell growth and productivity profiles deviated from the control condition. Further, charge variants (main, acidic, basic species) and glycosylation (G0F, afucosylation, and high mannose) were examined. Statistically significant differences were observed for one or more of these quality attributes with any shifts in media preparation. In this study, we demonstrated strong associations between media preparation conditions and cell growth, productivity, and product quality. The rapid evaluation of media by PAT implementation enabled more comprehensive understanding of different parameters on media quality and consequential effects on CHO cell culture.

10.
Cardiovasc Diabetol ; 23(1): 139, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664790

RESUMO

BACKGROUND: Diabetic cardiomyopathy (DCM) poses a growing health threat, elevating heart failure risk in diabetic individuals. Understanding DCM is crucial, with fibroblasts and endothelial cells playing pivotal roles in driving myocardial fibrosis and contributing to cardiac dysfunction. Advances in Multimodal single-cell profiling, such as scRNA-seq and scATAC-seq, provide deeper insights into DCM's unique cell states and molecular landscape for targeted therapeutic interventions. METHODS: Single-cell RNA and ATAC data from 10x Multiome libraries were processed using Cell Ranger ARC v2.0.1. Gene expression and ATAC data underwent Seurat and Signac filtration. Differential gene expression and accessible chromatin regions were identified. Transcription factor activity was estimated with chromVAR, and Cis-coaccessibility networks were calculated using Cicero. Coaccessibility connections were compared to the GeneHancer database. Gene Ontology analysis, biological process scoring, cell-cell communication analysis, and gene-motif correlation was performed to reveal intricate molecular changes. Immunofluorescent staining utilized various antibodies on paraffin-embedded tissues to verify the findings. RESULTS: This study integrated scRNA-seq and scATAC-seq data obtained from hearts of WT and DCM mice, elucidating molecular changes at the single-cell level throughout the diabetic cardiomyopathy progression. Robust and accurate clustering analysis of the integrated data revealed altered cell proportions, showcasing decreased endothelial cells and macrophages, coupled with increased fibroblasts and myocardial cells in the DCM group, indicating enhanced fibrosis and endothelial damage. Chromatin accessibility analysis unveiled unique patterns in cell types, with heightened transcriptional activity in myocardial cells. Subpopulation analysis highlighted distinct changes in cardiomyocytes and fibroblasts, emphasizing pathways related to fatty acid metabolism and cardiac contraction. Fibroblast-centered communication analysis identified interactions with endothelial cells, implicating VEGF receptors. Endothelial cell subpopulations exhibited altered gene expressions, emphasizing contraction and growth-related pathways. Candidate regulators, including Tcf21, Arnt, Stat5a, and Stat5b, were identified, suggesting their pivotal roles in DCM development. Immunofluorescence staining validated marker genes of cell subpopulations, confirming PDK4, PPARγ and Tpm1 as markers for metabolic pattern-altered cardiomyocytes, activated fibroblasts and endothelial cells with compromised proliferation. CONCLUSION: Our integrated scRNA-seq and scATAC-seq analysis unveils intricate cell states and molecular alterations in diabetic cardiomyopathy. Identified cell type-specific changes, transcription factors, and marker genes offer valuable insights. The study sheds light on potential therapeutic targets for DCM.


Assuntos
Cardiomiopatias Diabéticas , Análise de Célula Única , Transcriptoma , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/fisiopatologia , Animais , Perfilação da Expressão Gênica , Cromatina/metabolismo , Cromatina/genética , Camundongos Endogâmicos C57BL , Redes Reguladoras de Genes , Montagem e Desmontagem da Cromatina , Modelos Animais de Doenças , Masculino , RNA-Seq , Regulação da Expressão Gênica , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose , Camundongos , Células Endoteliais/metabolismo , Células Endoteliais/patologia
11.
ACS Cent Sci ; 10(4): 775-781, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38680569

RESUMO

Imine-linked covalent organic frameworks (COFs) usually show high crystallinity and porosity, while vinyl-linked COFs have excellent semiconducting properties and stability. Therefore, achieving the advantages of imine- and vinyl-linkages in a single COF material is highly interesting but remains challenging. Herein, we demonstrate the fabrication of a layer-blocked COF (LB-COF) heterogeneous film that is composed of imine- and vinyl-linkages through two successive surface-initiated polycondensations. In brief, the bottom layer of imine-linked COF film was constructed on an amino-functionalized substrate via Schiff-base polycondensation, in which the unreacted aldehyde edges could be utilized for initiating aldol polycondensation to prepare the second layer of vinyl-linked COF film. The resultant LB-COF film displays excellent ordering due to the crystalline templating effect from the bottom imine-linked COF layer; meanwhile, the upper vinyl-linked COF layer could strongly enhance its stability and photocatalytic properties. The LB COF also presents superior performance in photocatalytic uranium extraction (320 mg g-1), which is higher than the imine-linked (35 mg g-1) and the vinyl-linked (295 mg g-1) counterpart. This study provides a novel surface-initiated strategy to synthesize layer-blocked COF heterogeneous films that combine the advantages of each building block.

12.
Front Endocrinol (Lausanne) ; 15: 1339731, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464969

RESUMO

Background: The association between the sensorineural hearing loss (SNHL) and triglyceride-glucose (TyG) index remains inadequately understood. This investigation seeks to elucidate the connection between the TyG index and SNHL. Methods: In this cross-sectional study, we utilized datasets sourced from the National Health and Nutrition Examination Survey (NHANES). A comprehensive analysis was conducted on 1,851 participants aged 20 to 69, utilizing complete audiometry data from the NHANES database spanning from 2007 to 2018. All enrolled participants had accessible hearing data, and the average thresholds were measured and calculated as both low-frequency pure-tone average and high-frequency pure-tone average. Sensorineural hearing loss (SNHL) was defined as an average pure tone of 20 dB or higher in at least one better ear. Our analysis involved the application of multivariate linear regression models to examine the linear relationship between the TyG index and SNHL. To delineate any non-linear associations, we utilized fitted smoothing curves and conducted threshold effect analysis. Furthermore, we conducted a two-sample Mendelian randomization (MR) study, leveraging genetic data from genome-wide association studies (GWAS) on circulating lipids, blood glucose, and SNHL. The primary analytical method for the MR study was the application of the inverse-variance-weighted (IVW) approach. Results: In our multivariate linear regression analysis, a substantial positive correlation emerged between the TyG index and SNHL [2.10 (1.80-2.44), p < 0.0001]. Furthermore, using a two-segment linear regression model, we found an L-shaped relationship between TyG index, fasting blood glucose and SNHL with an inflection point of 9.07 and 94 mg/dL, respectively. Specifically, TyG index [3.60, (1.42-9.14)] and blood glucose [1.01, (1.00-1.01)] concentration higher than the threshold values was positively associated with SNHL risk. Genetically determined triglyceride levels demonstrated a causal impact on SNHL (OR = 1.092, p = 8.006 × 10-4). In addition, blood glucose was found to have a protective effect on SNHL (OR = 0.886, p = 1.012 × 10-2). Conclusions: An L-shaped association was identified among the TyG index, fasting blood glucose, and SNHL in the American population. TyG index of more than 9.07 and blood glucose of more than 94 mg/dL were significantly and positively associated with SNHL risk, respectively.


Assuntos
Perda Auditiva Neurossensorial , Análise da Randomização Mendeliana , Humanos , Estados Unidos , Inquéritos Nutricionais , Estudos Transversais , Triglicerídeos , Glucose , Glicemia , Estudo de Associação Genômica Ampla , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/diagnóstico
13.
Artigo em Chinês | MEDLINE | ID: mdl-38297876

RESUMO

Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease in otorhinolaryngology, in which eosinophilic chronic rhinosinusitis with nasal polyps represents the difficult-to-treat chronic rhinosinusitis (DTCRS) with poor prognosis. DTCRS has a poor prognosis, which seriously affects people's physical and mental health, and is treated with various means, including medication, biotherapy and surgery. In recent years, endoscopic sinus surgery and postoperative local administration of nasal hormones as one of its treatment methods have achieved good results. In this paper, we review the relevant literature at home and abroad and give an overview for the treatment means of surgery, focusing on the effect of endoscopic sinus surgery on the distributable range of postoperative nasal glucocorticosteroids in patients with DTCRS, and then on the postoperative efficacy of the treatment, with a view to providing a reference for the clinical treatment of DTCRS.


Assuntos
Pólipos Nasais , Seios Paranasais , Rinite , Sinusite , Humanos , Rinite/terapia , Seios Paranasais/cirurgia , Sinusite/terapia , Corticosteroides/uso terapêutico , Pólipos Nasais/cirurgia , Doença Crônica
14.
J Am Chem Soc ; 146(2): 1318-1325, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38181378

RESUMO

Sp2-carbon-conjugated covalent organic frameworks (sp2c-COFs) have emerged as promising platforms for phototo-chemical energy conversion due to their tailorable optoelectronic properties, in-plane π-conjugations, and robust structures. However, the development of sp2c-COFs in photocatalysis is still highly hindered by their limited linkage chemistry. Herein, we report a novel thiadiazole-bridged sp2c-COF (sp2c-COF-ST) synthesized by thiadiazole-mediated aldol-type polycondensation. The resultant sp2c-COF-ST demonstrates high chemical stability under strong acids and bases (12 M HCl or 12 M NaOH). The electro-deficient thiadiazole together with fully conjugated and planar skeleton endows sp2c-COF-ST with superior photoelectrochemical performance and charge-carrier separation and migration ability. As a result, when employed as a photocathode, sp2c-COF-ST exhibits a significant photocurrent up to ∼14.5 µA cm-2 at 0.3 V vs reversible hydrogen electrode (RHE) under visible-light irradiation (>420 nm), which is much higher than those analogous COFs with partial imine linkages (mix-COF-SNT ∼ 9.5 µA cm-2) and full imine linkages (imi-COF-SNNT ∼ 4.9 µA cm-2), emphasizing the importance of the structure-property relationships. Further temperature-dependent photoluminescence spectra and density functional theory calculations demonstrate that the sp2c-COF-ST has smaller exciton binding energy as well as effective mass in comparison to mix-COF-SNT and imi-COF-SNNT, which suggests that the sp2c-conjugated skeleton enhances the exciton dissociation and carrier migration under light irradiation. This work highlights the design and preparation of thiadiazole-bridged sp2c-COFs with promising photocatalytic performance.

15.
Anal Chem ; 96(3): 1102-1111, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38179931

RESUMO

Extracellular matrix (ECM) stiffness modulates a variety of cellular processes, including ferroptosis, a process with significant potential implications for hepatocellular carcinoma (HCC) fibrosis and cirrhosis. However, the exact relationship between ECM stiffness and HCC ferroptosis is yet unclarified, partially due to the lack of in situ information on key parameters of the ferroptosis process of living HCC cells. This study pioneers the use of in vitro mechanical microenvironment models of HCC and the scanning electrochemical microscopy (SECM) technique for understanding this interplay. We first cultured HuH7 cells on 4.0, 18.0, and 44.0 kPa polyacrylamide (PA) gels to simulate early, intermediate, and advanced HCC ECM stiffness, respectively. Then, we used SECM to in situ monitor changes in cell membrane permeability, respiratory activity, and reactive oxygen species (ROS) levels of erastin-induced HuH7 cells on PA gels, finding that increasing ECM stiffness potentiates ferroptosis, including increased membrane permeabilization and H2O2 release as well as reduced respiratory activity. Through further transcriptome sequencing and molecular biology measurements, we identified a critical role for focal adhesion kinase (FAK)-mediated yes-associated protein (YAP) in regulating the ferroptosis process dependent on ECM stiffness, which provides novel insights into the mechanical regulation of ferroptosis in HCC cells and may pave the way for innovative therapeutic strategies.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patologia , Peróxido de Hidrogênio/metabolismo , Microscopia Eletroquímica de Varredura , Matriz Extracelular/metabolismo , Fibrose , Géis/metabolismo , Microambiente Tumoral
16.
Biotechnol Prog ; 40(2): e3424, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38178645

RESUMO

The previous research showcased a partial least squares (PLS) regression model accurately predicting cell death percentages using in-line capacitance spectra. The current study advances the model accuracy through adaptive modeling employing a data fusion approach. This strategy enhances prediction performance by incorporating variables from the Cole-Cole model, conductivity and its derivatives over time, and Mahalanobis distance into the predictor matrix (X-matrix). Firstly, the Cole-Cole model, a mechanistic model with parameters linked to early cell death onset, was integrated to enhance prediction performance. Secondly, the inclusion of conductivity and its derivatives over time in the X-matrix mitigated prediction fluctuations resulting from abrupt conductivity changes during process operations. Thirdly, Mahalanobis distance, depicting spectral changes relative to a reference spectrum from a previous time point, improved model adaptability to independent test sets, thereby enhancing performance. The final data fusion model substantially decreased root-mean squared error of prediction (RMSEP) by around 50%, which is a significant boost in prediction accuracy compared to the prior PLS model. Robustness against reference spectrum selection was confirmed by consistent performance across various time points. In conclusion, this study illustrates that the data fusion strategy substantially enhances the model accuracy compared to the previous model relying solely on capacitance spectra.


Assuntos
Apoptose , Análise Espectral , Análise dos Mínimos Quadrados
17.
Nat Microbiol ; 9(2): 464-476, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38228857

RESUMO

Methane-dependent nitrate and nitrite removal in anoxic environments is thought to rely on syntrophy between ANME-2d archaea and bacteria in the genus 'Candidatus Methylomirabilis'. Here we enriched and purified a single Methylomirabilis from paddy soil fed with nitrate and methane, which is capable of coupling methane oxidation to nitrate reduction via nitrite to dinitrogen independently. Isotope labelling showed that this bacterium we name 'Ca. Methylomirabilis sinica' stoichiometrically performed methane-dependent complete nitrate reduction to dinitrogen gas. Multi-omics analyses collectively demonstrated that 'M. sinica' actively expressed a well-established pathway for this process, especially including nitrate reductase Nap. Furthermore, 'M. sinica' exhibited a higher nitrate affinity than most denitrifiers, implying its competitive fitness under oligotrophic nitrogen-limited conditions. Our findings revise the paradigm of methane-dependent denitrification performed by two organisms, and the widespread presence of 'M. sinica' in public databases suggests that the coupling of methane oxidation and complete denitrification in single cells substantially contributes to global methane and nitrogen budgets.


Assuntos
Nitratos , Nitritos , Nitritos/metabolismo , Nitratos/metabolismo , Desnitrificação , Metano/metabolismo , Anaerobiose , Bactérias/metabolismo , Nitrogênio/metabolismo
18.
Bioresour Technol ; 393: 130050, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37989420

RESUMO

Traditional unidirectional ventilation often leads to the loss of heat and moisture during composting, disrupting the favorable microenvironment required for aerobic microbes. This study developed a pulse alternating ventilation composting reactor and investigated the effects of alternating ventilation on composting efficiency compared with upward ventilation and downward ventilation. The results demonstrated that alternating ventilation stabilized the moisture content at approximately 60 % while reducing the temperature and oxygen concentration range within the reactor. Moreover, it extended the duration of high-temperature (>50 °C) by 31 % and 75 % compared to other two groups. It improved the microbial cooperation intensity and stimulated the core microbe (Tepidimicrobium). Seed germination index (GI) of the compost was improved (GI = 91.27 %), and the humic acid content was 1.23 times and 1.37 times higher than other two groups. These results showed that alternating ventilation can be used for efficient resource disposal of food waste.


Assuntos
Compostagem , Eliminação de Resíduos , Eliminação de Resíduos/métodos , Perda e Desperdício de Alimentos , Alimentos , Temperatura , Oxigênio , Solo
19.
J Hazard Mater ; 465: 133241, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38101009

RESUMO

Arsenic (As) is a toxic metalloid that poses a potential risk to the environment and human health. In this study, drinking water treatment residue (DWTR) and ceramsite-based vertical flow constructed wetlands (VFCWs) were built to purify As-containing wastewater. As a method of bioaugmentation, arbuscular mycorrhizal fungi (AMF) was inoculated to Pteris vittata roots to enhance the As removal of the VFCWs. The results showed that the As removal rates reached 87.82-94.29% (DWTR) and 33.28-58.66% (ceramsite). DWTR and P. vittata contributed 64.33-72.07% and 7.57-29% to the removal of As, while AMF inoculation intensified the As accumulation effect of P. vittata. Proteobacteria, the main As3+ oxidizing bacteria in the aquatic systems, dominated the microbial community, occupying 72.41 ± 7.76%. AMF inoculation increased As-related functional genes abundance in DWTR-based wetlands and provided a reliable means of arsenic resistance in wetlands. These findings indicated that the DWTR-based VFCWs with AMF inoculated P. vittata had a great purification effect on As-containing wastewater, providing a theoretical basis for the application of DWTR and AMF for As removal in constructed wetlands.


Assuntos
Arsênio , Água Potável , Micorrizas , Humanos , Águas Residuárias , Áreas Alagadas , Raízes de Plantas/microbiologia
20.
Chem Sci ; 15(1): 171-184, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38131065

RESUMO

Microglia play a crucial role in maintaining the homeostasis of the central nervous system (CNS) by sensing and responding to mechanical and inflammatory cues in their microenvironment. However, the interplay between mechanical and inflammatory cues in regulating microglia activation remains elusive. In this work, we constructed in vitro mechanical-inflammatory coupled microenvironment models of microglia by culturing BV2 cells (a murine microglial cell line) on polyacrylamide gels with tunable stiffness and incorporating a lipopolysaccharide (LPS) to mimic the physiological and pathological microenvironment of microglia in the hippocampus. Through characterization of activation-related proteins, cytokines, and reactive oxygen species (ROS) levels, we observed that the LPS treatment induced microglia on a stiff matrix to exhibit overexpression of NOX2, higher levels of ROS and inflammatory factors compared to those on a soft matrix. Additionally, using scanning electrochemical microscopy (SECM), we performed in situ characterization and discovered that microglia on a stiff matrix promoted extracellular ROS production, leading to a disruption in their redox balance and increased susceptibility to LPS-induced ROS production. Furthermore, the respiratory activity and migration behavior of microglia were closely associated with their activation process, with the stiff matrix-LPS-induced microglia demonstrating the most pronounced changes in respiratory activity and migration ability. This work represents the first in situ and dynamic monitoring of microglia activation state alterations under a mechanical-inflammatory coupled microenvironment using SECM. Our findings shed light on matrix stiffness-dependent activation of microglia in response to an inflammatory microenvironment, providing valuable insights into the mechanisms underlying neuroinflammatory processes in the CNS.

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